Men who have sex with men (MSM) constitute a substantial proportion of the Indian HIV-seropositive population. The incidence of human papillomavirus (HPV)-related malignancies and their precursor lesions is increased in HIV-seropositive MSM including cancers of the anus and penis. We recently completed a cross-sectional study of HPV infection in 300 HIV-seropositive MSM at Humsafar Trust in Mumbai and Christian Medical College (CMC) in Vellore and showed that the prevalence of anogenital HPV infection in this population is very high. However, little is known of the incidence of anogenital HPV- associated disease in this population. We now propose to extend our cross-sectional analysis to study the incidence of anogenital HPV infection and HPV-associated disease in 246 Indian HIV-seropositive MSM. Our specific aims are: 1) Determine the prevalence and incidence of HPV-associated premalignant lesions in the anus and penis in Indian HIV-seropositive men MSM;2) Describe risk factors for prevalent premalignant lesions in the anus and penis in Indian HIV-seropositive MSM;and 3) Describe the incidence of penile and anal HPV infection in Indian HIV-seropositive MSM. Men will be followed over one year at 6-month intervals for a total of 3 visits. At each visit 123 HIV-seropositive men at each site will be administered a questionnaire. HPV DNA samples will be collected from the anus and penis. Blood will be obtained for CD4+ at all visits and HIV viral load levels at baseline and 12 months. Anal cytology and high resolution anoscopy will be performed with biopsy of visible anal lesions. Penile exams and biopsies will also be performed. HPV DNA testing will be performed at CMC Vellore. Training and quality assurance will be performed at the UCSF. Data from this study will be important for the care of both men and women in India overall, since many Indian MSM have female sexual partners, and HIV-seropositive men may serve as a bridge population to women. Knowledge of HPV-related precancerous disease will be important to planning cancer prevention efforts in HIV-seropositive individuals in India since these HPV-related cancers may be preventable. Data on HPV infection will contribute to the development of optimal next-generation vaccines. This study builds upon a growing collaboration between UCSF, CMC Vellore, Humsafar Trust and the AIDS Malignancy Consortium. It will lead to capacity-building and many additional studies of HPV and associated diseases in India. PUBLIC HEALTH RELEVANCE: The incidence of human papillomavirus (HPV)-related cancers is likely to be increased among Indian HIV-seropositive men who have sex with men (MSM) and we have shown that anogenital HPV infection is very common among Indian HIV-seropositive MSM. However, nothing is known about HPV-related disease including precancerous lesions in this population and since these cancers may be preventable, we will determine how common these lesions are, learn about risk factors, and determine how commonly they develop over a one-year period.